KML001, a Telomere-Targeting Drug, Sensitizes Glioblastoma Cells to Temozolomide Chemotherapy and Radiotherapy through DNA Damage and Apoptosis
Joint Authors
Woo, Seon Rang
Ham, Yunhee
Kang, Wonyoung
Yang, Heekyoung
Kim, Sujong
Jin, Juyoun
Joo, Kyeung Min
Nam, Do-Hyun
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-09-10
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Standard treatment for glioblastoma comprises surgical resection, chemotherapy with temozolomide, and radiotherapy.
Nevertheless, majority of glioblastoma patients have recurrence from resistance to the cytotoxic conventional therapies.
We examined combinational effects of KML001, an arsenic compound targeting telomeres of chromosomes with temozolomide or irradiation, in glioblastoma cell lines and xenograft models, to overcome the therapeutic limitation of chemoradiation therapy for glioblastoma.
Although KML001 alone showed little effects on in vitro survival of glioblastoma cells, cell death by in vitro temozolomide treatment or irradiation was synergistically potentiated by combination with KML001.
Since phosphorylated γ-H2AX, cleaved casepase-3, and cleaved PARP were dramatically increased by KML001, the synergistic effects would be mediated by increased DNA damage and subsequent tumor cell apoptosis.
Combinatorial effects of KML001 were observed not only in chemo- and radiosensitive glioblastoma cell line, U87MG, but also in the resistant cell line, U251MG.
In the U87MG glioblastoma xenograft models, KML001 did not have systemic toxicity but showed synergistic therapeutic effects in combination with temozolomide or irradiation to reduce tumor volumes significantly.
These data indicated that KML001 could be a candidate sensitizer to potentiate therapeutic effects of conventional cytotoxic treatment for glioblastoma.
American Psychological Association (APA)
Woo, Seon Rang& Ham, Yunhee& Kang, Wonyoung& Yang, Heekyoung& Kim, Sujong& Jin, Juyoun…[et al.]. 2014. KML001, a Telomere-Targeting Drug, Sensitizes Glioblastoma Cells to Temozolomide Chemotherapy and Radiotherapy through DNA Damage and Apoptosis. BioMed Research International،Vol. 2014, no. 2014, pp.1-10.
https://search.emarefa.net/detail/BIM-1016535
Modern Language Association (MLA)
Woo, Seon Rang…[et al.]. KML001, a Telomere-Targeting Drug, Sensitizes Glioblastoma Cells to Temozolomide Chemotherapy and Radiotherapy through DNA Damage and Apoptosis. BioMed Research International No. 2014 (2014), pp.1-10.
https://search.emarefa.net/detail/BIM-1016535
American Medical Association (AMA)
Woo, Seon Rang& Ham, Yunhee& Kang, Wonyoung& Yang, Heekyoung& Kim, Sujong& Jin, Juyoun…[et al.]. KML001, a Telomere-Targeting Drug, Sensitizes Glioblastoma Cells to Temozolomide Chemotherapy and Radiotherapy through DNA Damage and Apoptosis. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-10.
https://search.emarefa.net/detail/BIM-1016535
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1016535